This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overall aim of the project is to develop procedures whereby adult stem cells from the bone marrow stroma can be used for trials of gene therapy in non-human primates. The adult stem cells, referred to as mesenchymal stem cells or marrow stromal cells (MSCs), are of interest for cell and gene therapy because they can readily be obtained from a patient, expanded in culture, genetically engineered with or without the use of viruses, and then returned for therapy of the same patient. They are also of interest because they home to damaged tissues and differentiate to replace the damaged cells in the tissues. The cells are currently being tested in many small animal models of human diseases and several promising clinical trials with the cells have been initiated in rare diseases in children. However, extensive trials of the cells in non-human primates are clearly essential for some of the currently proposed applications to common diseases such as osteoporosis, cardiac failure, Parkinsonism, leukodystrophies, and Alzheimer's disease. The goals of the proposal are: Specific Aim. Compare the primate MSCs to human MSCs in vivo in their ability to engraft into multiple tissues after systemic or intracranial infusion into immunodeficient mice. These studies are currently ongoing. We have injected human and rhesus bone marrow and adipose tissue derived MSCs into the CNS of NIHIII and Twitcher (Krabbe-affected) mice, using stereotaxic delivery. We are currently assessing engraftment and differentiation of these cells in the CNS. Data from the immune deficient mice indicate the cells engraft, persist for as long as 180 days and undergo moderate differentiation along neural lineages. Direct injection of MSCs (derived from bone marrow and adipose tissue) into the lateral ventricles of the brains of Twitcher mice is currently being collected. To date, we have demonstrated a statistically significant increase in life span in Krabbe-affected animals. The primary mechanisms by which the cells appear to mediate the effect is through suppression of the inflammatory pathways associated with the disease. We have also begun applying these cells for other diseases such as Multiple Sclerosis and Type II diabetes.